This is a research program begun in 1955 to gain fundamental information about the mechanism of action of purine and pyrimidine analogs and about the enzymes and cell types with which these analogs or their derivatives interact: 1. Enzymes of purine nucleotide metabolism. Included will be studies of the enzymes: Human erythrocytic adenosine deaminase, adenosine kinase, nucleoside diphosphokinase and ATP:GMP phosphotransferase. Considerable attention will be devoted to tight-binding inhibitors of adenosine deaminase, both with the purified enzyme and in intact cells. 2. Incorporation of natural and analog purines into the formed elements of blood. Studies will continue with the incorporation of various natural and analog purine nucleosides into the nucleotide pools of erythrocytes and platelets, and similar preliminary studies with lymphocytes will be expanded. Also, in the near future we hope to undertake further studies of the nucleotide metabolism of human granulocytes. 3. We will examine whether the adenylate cycle, which is important in the amino acid metabolism of muscle, plays a similar role in tumor cells and leucocytes. The effects of the incorporation of anti-metabolites, such as 6-mercaptopurine and 2-fluoroadenine, into the nucleotide pools will be studied. In other investigations, various purine nucleoside analogs, e.g. those of the 6-selenopurine and adenine series, will be examined for their interaction with enzymes of purine metabolism and for incorporation into the nucleotide pools of cells. 4. Species differences in purine metabolism. Along with our studies of human erythrocytes we plan to continue examinations of purine metabolism of erythrocytes of other species emphasizing those of commonly used laboratory animals where marked differences have already been detected. In addition, we plan to continue collaborative studies with the group of Professor A.W. Senft on the purine metabolism of the tropical disease agent Schistosoma mansoni.